Autosomal recessive limb-girdle muscular dystrophy type 2E

General Information (adopted from Orphanet):

Synonyms, Signs: LGMD2E
Beta-sarcoglycanopathy
Limb-girdle muscular dystrophy due to beta-sarcoglycan deficiency
Number of Symptoms 28
OrphanetNr: 119
OMIM Id: 604286
ICD-10: G71.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.1
Inheritance: Autosomal recessive
25862795 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Autosomal recessive limb-girdle muscular dystrophy
 -Rare genetic disease
 -Rare neurologic disease
Neuromuscular disease with dilated cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Qualitative or quantitative defects of beta-sarcoglycan
 -Rare genetic disease

Comment:

In this study comprising 32 patients, the authors described c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. Beta-sarcoglycan is essential for the formation of the beta/delta-sarcoglycan core structure, and disruption of this core affects targeting of the sarcoglycan complex to the plasma membrane, which explains the lack of the complex in muscle biopsies (PMID:25862795).

Symptom Information: Sort by abundance 

1
 (HPO:0002093) Respiratory insufficiency Occasional [IBIS] 19% (n=32) 25862795 IBIS 410 / 7739
2
 (HPO:0011675) Arrhythmia Occasional [IBIS] 28% (n=32) 25862795 IBIS 226 / 7739
3
 (HPO:0001962) Palpitations Frequent [IBIS] 31% (n=32) 25862795 IBIS 62 / 7739
4
 (HPO:0003236) Elevated serum creatine phosphokinase 25862795 IBIS 214 / 7739
5
 (HPO:0000969) Edema Occasional [IBIS] 19% (n=32) 25862795 IBIS 117 / 7739
6
 (HPO:0006785) Limb-girdle muscular dystrophy 25862795 IBIS 14 / 7739
7
 (HPO:0007126) Proximal amyotrophy 25862795 IBIS 29 / 7739
8
 (HPO:0000158) Macroglossia Frequent [IBIS] 31% (n=32) 25862795 IBIS 119 / 7739
9
 (HPO:0003327) Axial muscle weakness Frequent [IBIS] 88% (n=32) 25862795 IBIS 10 / 7739
10
 (HPO:0002460) Distal muscle weakness 25862795 IBIS 122 / 7739
11
 (HPO:0003325) Limb-girdle muscle weakness 25862795 IBIS 22 / 7739
12
 (HPO:0003701) Proximal muscle weakness Very frequent [IBIS] 100% (n=32) 25862795 IBIS 105 / 7739
13
 (HPO:0003326) Myalgia Frequent [IBIS] 31% (n=32) 25862795 IBIS 143 / 7739
14
 (HPO:0001288) Gait disturbance Frequent [IBIS] 34% (n=32) 25862795 IBIS 318 / 7739
15
 (HPO:0002015) Dysphagia Occasional [IBIS] 3 % (n=32) 25862795 IBIS 301 / 7739
16
 (HPO:0001771) Achilles tendon contracture Frequent [IBIS] 69% (n=32) 25862795 IBIS 27 / 7739
17
 (HPO:0003691) Scapular winging Frequent [IBIS] 59% (n=32) 25862795 IBIS 51 / 7739
18
 (HPO:0002650) Scoliosis Frequent [IBIS] 59% (n=32) 25862795 IBIS 705 / 7739
19
 (HPO:0000939) Osteoporosis Occasional [IBIS] 22% (n=32) 25862795 IBIS 129 / 7739
20
 (HPO:0001639) Hypertrophic cardiomyopathy Occasional [IBIS] 6% (n=32) 25862795 IBIS 137 / 7739
21
 (HPO:0001644) Dilated cardiomyopathy Occasional [IBIS] 19% (n=32) 25862795 IBIS 141 / 7739
22
 (HPO:0003707) Calf muscle pseudohypertrophy Frequent [IBIS] 78% (n=32) 25862795 IBIS 8 / 7739
23
 (HPO:0008988) Pelvic girdle muscle atrophy 25862795 IBIS 5 / 7739
24
 (HPO:0030107) Reduced muscle fiber beta sarcoglycan 25862795 IBIS 1 / 7739
25
 (HPO:0030051) Tip-toe gait Frequent [IBIS] 56% (n=32) 25862795 IBIS 10 / 7739
26
 (OMIM) Muscle weakness, proximal, limb-girdle 25862795 IBIS 1 / 7739
27
 (OMIM) Skeletal muscle shows decreased sarcoglycan proteins 25862795 IBIS 1 / 7739
28
 (OMIM) Skeletal muscle shows dystrophic changes 25862795 IBIS 1 / 7739

Associated genes:

SGCB;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
SGCB rs104893868 pathogenic RCV000009251.3
SGCB rs104893869 pathogenic RCV000009254.3
SGCB rs104893869 pathogenic RCV000009257.3
SGCB rs104893870 pathogenic RCV000009255.5
SGCB rs104893871 pathogenic RCV000009256.5
SGCB rs150518260 pathogenic RCV000177020.2
SGCB rs28936383 pathogenic RCV000009250.3
SGCB rs398123262 pathogenic RCV000173087.1
SGCB rs796065319 pathogenic RCV000173088.1

Additional Information:

Diagnosis OMIM - Prenatal Diagnosis

Pegoraro et al. (1999) reported the first prenatal diagnosis of LGMD2E by direct gene mutation detection.
Clinical Description OMIM Jackson and Strehler (1968) reported 5 nuclear Old Amish families from southern Indiana with autosomal recessive limb-girdle muscular dystrophy. The families showed links to an ancestral couple born in the late 1700s (Allamand et al., 1995). In 6 Amish ...
Genotype-Phenotype Correlations OMIM Passos-Bueno et al. (1999) studied 140 patients from 40 Brazilian families with one of 7 autosomal recessive limb-girdle muscular dystrophies (LGMDs). All LGMD2E and LGMD2F (601287) patients had a severe phenotype; considerable inter- and intrafamilial variability was observed in ...
Molecular genetics OMIM In affected members of several Amish families with autosomal recessive LGMD, Lim et al. (1995) identified a homozygous mutation in the SGCB gene (600900.0001). Skeletal muscle biopsy showed a dramatic reduction in SGCB expression in the sarcolemma and a ...
Population genetics OMIM Jackson and Carey (1961) reported autosomal recessive limb-girdle muscular dystrophy in 7 nuclear families among the Old Order Amish in northern Indiana. The maternal and paternal lines had common ancestors: 2 brothers married sisters in the early 1800s. These ...